Diclofenac transdermal patch versus the sustained release tablet: A randomized clinical trial in rheumatoid arthritic patients

Purpose: To prepare and characterize transdermal films of diclofenac diethanolamine as a safer and more effective alternative than the sustained release (SR) tablet equivalent for prolonged relief from pain and inflammation in arthritis.Methods: Transdermal films of diclofenac were prepared using sodium carboxymethyl cellulose and polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. The films were characterized for  physicochemical properties and for ex vivo permeation in a randomized clinical trial(RCT) for analgesic activities in arthritic patients.Results: The transdermal films were uniform in weight and thickness, flat, with high drug content (94.40 ± 1.04 to 98.62 ± 1.08 %) and with high folding endurance (149 ± 9.09 to 192 ± 10.12). Drug permeation through excised rat abdominal skin was prolonged. Films containing penetration enhancers showed higher ex vivo drug permeation than those without the enhancer; furthermore, drug permeation increased with increase in the concentration of enhancer. The films were  non-irritating to the skin. In RCT, F3 (containing turpentine oil, 1 %v/w) decreased the pain score from 9.87 ± 1.14 to 4.94 ± 0.78 units, compared with the SR tablet (once daily) which decreased pain from 9.59 ± 0.42 to 6.49 ± 1.20 units, 48 h post-administration. Turpentine oil showed better permeation enhancement than sesame oil in the transdermal films.Conclusion: Transdermal films of diclofenac, formulated with permeation enhancers, may have greater therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of patient compliance in rheumatoid arthritis.Keywords: Analgesic activity, Diclofenac, Permeation enhancer, Rheumatoid arthritis, Transdermal film

Obstetric and perinatal outcomes of dizygotic twin pregnancies resulting from in vitro fertilization versus spontaneous conception: a retrospective study

This study was designed to to assess perinatal and neonatal outcomes of dizygotic twin pregnancies conceived naturally or by in vitro fertilization (IVF). After strict selection, the study included 470 dizygotic twin pregnancies. There were 249 resulting from IVF treatments and 221 conceiving spontaneously. After adjusting maternal age and primiparity, the results showed that there were no significant differences between the two groups (P > 0.05) in terms of maternal antenatal complications and neonatal outcomes. In conclusion, our study does not reveal increased risks for pregnancy-related complications and adverse neonatal outcomes in dizygotic twin pregnancies following IVF treatments. With these fundamental data, this study could provide a reference for perinatal care and clinical assisted reproductive technology (ART) treatment and help to inform infertile parents about the potential risks of IVF treatments

The association between alteration of maternal lipid levels and birthweight at term: A within-family comparison.

CONTEXT: Maternal lipid levels affect birthweight and the long-term health of the offsprings. However, this association could be influenced by genetic and other common factors. OBJECTIVE: This work aimed to explore the relationship between maternal lipid levels and birthweight of two pregnancies in the same mother. METHODS: In this population-based cohort study, 705 women and their 1 410 offsprings were included. From an initial sample of women with more than one singleton birth in the database, we made the following exclusions: missing data for pre-pregnancy BMI, pregnancy weight gain, birthweight and lipid values; maternal age less than 19 or older than 44 years old; gestational age 41weeks, gestational diabetes mellitus/diabetic. In the second and third trimesters, serum samples were collected for the determination of fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Then we assessed the association between maternal lipids and birthweight. RESULTS: Infants of women whose 2nd-trimester TC increased by 10th-20th percentile (-0.92~-0.56 mmol/L) from 1st to 2nd pregnancy were 239.69 (62.32~417.06) g lighter at birth than were infants of women those of 40th-50th percentile (-0.20~-0.03 mmol/L). Parity, gestational age, neonatal gender, maternal pre-pregnancy body mass index, maternal weight gain, and 3rd-trimester TC and HDL-C were all associated with higher birth weight. Every unit increase in TC in the third trimester increases birthweight by 53.13 (14.32 ~91.94) g. CONCLUSION: Maternal TC level is associated with birthweight independent of shared genes. TC may be used to guide diet and predict birthweight combined with ultrasound and other indicators

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Background/Aims: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and can cause heart failure, arrhythmia and sudden death. The pathogenesis of DCM includes altered metabolism, mitochondrial dysfunction, oxidative stress, inflammation, cell death and extracellular matrix remodeling. Recently, pyroptosis, a type of programmed cell death related to inflammation, was proven to be activated in DCM. However, the molecular mechanisms underlying pyroptosis in DCM remain elusive. The long non-coding RNA (lncRNA) Kcnq1ot1 participates in many cardiovascular diseases. This study aims to clarify whether Kcnq1ot1 affects cardiac pyroptosis in DCM. Methods: AC16 cells and primary cardiomyocytes were incubated with 5.5 and 50 mmol/L glucose. Diabetic mice were induced with streptozotocin (STZ). Kcnq1ot1 was silenced both in vitro and in vivo. qRT-PCR was used to detect the expression level of Kcnq1ot1. Immunofluorescence, qRT-PCR and western blot analyses were used to detect the degree of pyroptosis. Echocardiography, hematoxylin and eosin staining, and Masson’s trichrome staining were used to detect the cardiac function and morphology in mice. Cell death and function were detected using TUNEL staining, immunofluorescence staining and Ca2+ measurements. Results: The expression of Kcnq1ot1 was increased in patients with diabetes, high glucose-induced cardiomyocytes and diabetic mouse cardiac tissue. Silencing Kcnq1ot1 alleviated pyroptosis by targeting miR-214-3p and caspase-1. Furthermore, silencing Kcnq1ot1 reduced cell death, cytoskeletal structure abnormalities and calcium overload in vitro and improved cardiac function and morphology in vivo. Conclusion: Kcnq1ot1 is overexpressed in DCM, and silencing Kcnq1ot1 inhibits pyroptosis by influencing miR-214-3p and caspase-1 expression. We clarified for the first time that Kcnq1ot1 could be a new therapeutic target for DCM

Prevalence and prognostic significance of DNMT3A- and TET2- clonal haematopoiesis-driver mutations in patients presenting with ST-segment elevation myocardial infarction

Background Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Methods Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. Findings Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4–3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103–3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154–2.912, P = 0.010). Concentrations of plasma IL-1β (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group. Interpretation DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers

Yiqi Huoxue Recipe Improves Heart Function through Inhibiting Apoptosis Related to Endoplasmic Reticulum Stress in Myocardial Infarction Model of Rats

Objective. To explore the mechanism of cardioprotective effects of Chinese medicine, Yiqi Huoxue recipe, in rats with myocardial infarction- (MI-) induced heart failure. Methods. Male Sprague-Dawley rats underwent left anterior descending artery (LAD) ligation or sham operation. The surviving MI rats were divided randomly into three groups: MI (5 mL/kg/d NS by gavage), MI + Metoprolol Tartrate (MT) (12 mg/kg/d MT by gavage), and MI + Yiqi Huoxue (5 mL/kg recipe by gavage). And the sham operation rats were given 5 mL/kg/d normal saline. Treatments were given on the day following surgery for 4 weeks. Then rats were detected for heart structure and function by transthoracic echocardiography. Apoptosis in heart tissues was detected by TUNEL staining. To determine whether the endoplasmic reticulum (ER) stress response pathway is included in the cardioprotective function of the recipe, ER stress related proteins such as GRP78 and caspase-12 were examined. Results. Yiqi Huoxue recipe attenuated heart function injury, reversed histopathological damage, alleviated myocardial apoptosis and inhibited ER stress in MI rats. Conclusion. All the results suggest that Yiqi Huoxue recipe improves the injured heart function maybe through inhibition of ER stress response pathway, which is a promising target in therapy for heart failure